Aging of individuals and various diseases due to the aging are greatly involved with aging of all dividing cells (drop of dividing speed, drop of cell function). For example, skin includes epidermic cells, fibroblasts, and extracellular matrixes for supporting skin structures other than these cells, such as elastion and collagen. In young skin, interactivities between these skin tissues maintain homeostasis, which keeps moisture, flexibility, and resiliency. Consequently, skin appears to have tension and smoothness, and is kept fresh. However, aging, ultra-violet ray, dryness, stress etc. decrease functions of extracellular matrixes and fibroblasts in particular. Consequently, flexibility of skin and moisture-keeping function of skin drop, skin loses tension and smoothness, and senile symptoms such as chaps, wrinkles, and somberness appear.
In order to stop or prevent aging in cell level, activators and anti-aging agents have been searched. Known examples of activators derived from animals include hydrolysis of connective tissue (Patent Document 1), water-soluble protein derived from thymus gland and spleen (Patent Document 2), and essence of bovine placenta (Patent Document 3). Known examples of activators derived from plants include sesame, Chinese yam, pepper, angelica acutiloba, houttuynia, mondo grass (Patent Document 4), almond, taraxacum officinale, elder, Cnidium officinale, swertia japonica, morus ihou, inner core of seed of peach, ginseng, hop, althaea, and Job's tears. A part of these is used as an activator and an anti-aging agent in quail-drugs and cosmetics. However, an activator and an anti-aging agent that show satisfactory working effects are not yet obtained.
Mannosylerythritol lipid (MEL) is a natural surfactant produced by yeast, and it is reported that MEL has various physiological functions (Non-patent Document 1). Further, recently, mannosylmannitol lipid (MML) in which erythritol is replaced with mannitol has been found (Patent Document 9). As for usage as external medicines and cosmetics, effectiveness as an anti-inflammatory agent and an anti-allergy agent (Patent Document 10) and baldness remedy and hair growth (Patent Document 11), an anti-bacterial effect (Patent Document 12), and surface-tension-reduction function (Patent Document 13) are known.
However, activating function of MEL for cells has been completely unknown. Further, hair growth function described in Patent Document 11 was confirmed through animal experiments, and it has not been reported that MEL activates human head hair-papilla cells.
As described above, it is reported that a biosurfactant such as glycolipid has environment-friendly features such as high biodegradability and low toxicity, and has new physiological functions. In view of these features, widely applying a biosurfactant to food industry, cosmetic industry, medicine industry, chemical industry, and field of environment allows attaining a sustainable society and providing high-function products, and therefore very significant.
One of representative glycolipid biosurfactants is MEL. MEL is a material found from Ustilago nuda and Shizonella melanogramma (see Non-patent Documents 2 and 3). Later, it is reported that MEL can be produced by yeasts such as Candida yeast that is a mutated strain producing itaconic acid (see Patent Document 14 and Non-patent Document 4), Candida antarctia (currently called as Pseudozyma antarctica) (see Non-patent Documents 5 and 6), and Kurtzmanomyces yeast (see Non-patent Document 7). Nowadays, long-time continuous cultivation and production allows producing 300 g/L or more of MEL.
[Patent Document 1]
Japanese Unexamined Patent Publication No. Tokukaisho 62-84024
[Patent Document 2]
Japanese Unexamined Patent Publication No. Tokukaisho 63-188697
[Patent Document 3]
Japanese Unexamined Patent Publication No. Tokukaihei 03-141299
[Patent Document 4]
Japanese Unexamined Patent Publication No. Tokukaihei 10-45615
[Patent Document 5]
Japanese Unexamined Patent Publication No. Tokukaihei 10-036279
[Patent Document 6]
Japanese Unexamined Patent Publication No. Tokukaihei 10-36279
[Patent Document 7]
Japanese Unexamined Patent Publication No. Tokukai 2004-75632
[Patent Document 8]
Japanese Unexamined Patent Publication No. Tokukai 2005-89375
[Patent Document 9]
Japanese Unexamined Patent Publication No. Tokukai 2005-104837
[Patent Document 10]
Japanese Unexamined Patent Publication No. Tokukai 2005-68015
[Patent Document 11]
Japanese Unexamined Patent Publication No. Tokukai 2003-261424
[Patent Document 12]
Japanese Unexamined Patent Publication No. Tokukaisho 57-145896
[Patent Document 13]
Japanese Unexamined Patent Publication No. Tokukaisho 61-205450
[Patent Document 14]
Japanese Unexamined Patent Publication No. Tokukosho 57-145896
[Non-patent Document 1]
Journal of bioscience and bioengineering, 94, 187 (2002)
[Non-patent Document 2]
R. H. Haskins, J. A. Thorn, B. Boothroyd, Can. J. Microbiol., Vol 1, p749-756, 1955.
[Non-patent Document 3]
G. Deml, T. Anke, F. Oberwinkler, B. M. Giannetti, W. Steglich, Phytochemistry, Vol 19, p 83-87, 1980.
[Non-patent Document 4]
T. Nakahara, H. Kawasaki, T. Sugisawa, Y. Takamori, T. Tabuchi, J. Ferment. Technol. Vol61, p19-23, 1983.
[Non-patent Document 5]
D. Kitamoto, S. Akiba, C. Hioki, T. Tabuch, Agric. Biol. Chem., Vol 54. P31-36, 1990.
[Non-patent Document 6]
H.-S. Kim, B.-D. Yoon, D.-H. Choung, H.-M. Oh, T. Katsuragi, Y. Tani, Appl. Microbiol. Biotechnol., Springer-Verlag, Vol52, p713-721, 1999.
[Non-patent Document 7]
K. kakukawa, M. Tamai, K. Imamura, K. Miyamoto, S. Miyoshi, Y. Morinaga, O, Suzuki, T. Miyakawa, Biosci. Biotechnol. Biochem., Vol66, p188-191, 2002.
[Non-patent Document 8]
D. Crich, M. A. Mora, R. Cruz, Tetrahedron, Elsevier, Vol58, p35-44, 2002.
[Non-patent Document 9]
Dai Kitamoto, Oleoscience (Japan), Japan Oil Chemists' Society, Vol. 3, p663-672 (2003).
[Non-patent Document 10]
T. Imura, N. Ohta, K. Inoue, N. Yagi, H. Negishi, H. Yanagishita, D. Kitamoto, Chem. Eur. J, Wiley, Vol12, p2434-2440, 2006.